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Institut
- Psychologie (94) (entfernen)
Interaction between the Hypothalamic-Pituitary-Adrenal Axis and the Circadian Clock System in Humans
(2017)
Rotation of the Earth creates day and night cycles of 24 h. The endogenous circadian clocks sense these light/dark rhythms and the master pacemaker situated in the suprachiasmatic nucleus of the hypothalamus entrains the physical activities according to this information. The circadian machinery is built from the transcriptional/translational feedback loops generating the oscillations in all nucleated cells of the body. In addition, unexpected environmental changes, called stressors, also challenge living systems. A response to these stimuli is provided immediately via the autonomic-nervous system and slowly via the hypothalamus"pituitary"adrenal (HPA) axis. When the HPA axis is activated, circulating glucocorticoids are elevated and regulate organ activities in order to maintain survival of the organism. Both the clock and the stress systems are essential for continuity and interact with each other to keep internal homeostasis. The physiological interactions between the HPA axis and the circadian clock system are mainly addressed in animal studies, which focus on the effects of stress and circadian disturbances on cardiovascular, psychiatric and metabolic disorders. Although these studies give opportunity to test in whole body, apply unwelcome techniques, control and manipulate the parameters at the high level, generalization of the results to humans is still a debate. On the other hand, studies established with cell lines cannot really reflect the conditions occurring in a living organism. Thus, human studies are absolutely necessary to investigate mechanisms involved in stress and circadian responses. The studies presented in this thesis were intended to determine the effects of cortisol as an end-product of the HPA axis on PERIOD (PER1, PER2 and PER3) transcripts as circadian clock genes in healthy humans. The expression levels of PERIOD genes were measured under baseline conditions and after stress in whole blood. The results demonstrated here have given better understanding of transcriptional programming regulated by pulsatile cortisol at standard conditions and short-term effects of cortisol increase on circadian clocks after acute stress. These findings also draw attention to inter-individual variations in stress response as well as non-circadian functions of PERIOD genes in the periphery, which need to be examined in details in the future.
Numerous RCTs demonstrate that cognitive behavioral therapy (CBT) for depression is effective. However, these findings are not necessarily representative of CBT under routine care conditions. Routine care studies are not usually subjected to comparable standardizations, e.g. often therapists may not follow treatment manuals and patients are less homogeneous with regard to their diagnoses and sociodemographic variables. Results on the transferability of findings from clinical trials to routine care are sparse and point in different directions. As RCT samples are selective due to a stringent application of inclusion/exclusion criteria, comparisons between routine care and clinical trials must be based on a consistent analytic strategy. The present work demonstrates the merits of propensity score matching (PSM), which offers solutions to reduce bias by balancing two samples based on a range of pretreatment differences. The objective of this dissertation is the investigation of the transferability of findings from RCTs to routine care settings.
Educational assessment tends to rely on more or less standardized tests, teacher judgments, and observations. Although teachers spend approximately half of their professional conduct in assessment-related activities, most of them enter their professional life unprepared, as classroom assessment is often not part of their educational training. Since teacher judgments matter for the educational development of students, the judgments should be up to a high standard. The present dissertation comprises three studies focusing on accuracy of teacher judgments (Study 1), consequences of (mis-)judgment regarding teacher nomination for gifted programming (Study 2) and teacher recommendations for secondary school tracks (Study 3), and individual student characteristics that impact and potentially bias teacher judgment (Studies 1 through 3). All studies were designed to contribute to a further understanding of classroom assessment skills of teachers. Overall, the results implied that, teacher judgment of cognitive ability was an important constant for teacher nominations and recommendations but lacked accuracy. Furthermore, teacher judgments of various traits and school achievement were substantially related to social background variables, especially the parents" educational background. However, multivariate analysis showed social background variables to impact nomination and recommendation only marginally if at all. All results indicated differentiated but potentially biased teacher judgments to impact their far-reaching referral decisions directly, while the influence of social background on the referral decisions itself seems mediated. Implications regarding further research practices and educational assessment strategies are discussed. The implications on the needs of teachers to be educated on judgment and educational assessment are of particular interest and importance.
The Firepower of Work Craving: When Self-Control Is Burning under the Rubble of Self-Regulation
(2017)
Work craving theory addresses how work-addicted individuals direct great emotion-regulatory efforts to weave their addictive web of working. They crave work for two main emotional incentives: to overcompensate low self-worth and to escape (i.e., reduce) negative affect, which is strategically achieved through neurotic perfectionism and compulsive working. Work-addicted individuals" strong persistence and self-discipline with respect to work-related activities suggest strong skills in volitional action control. However, their inability to disconnect from work implies low volitional skills. How can work-addicted individuals have poor and strong volitional skills at the same time? To answer this paradox, we elaborated on the relevance of two different volitional modes in work craving: self-regulation (self-maintenance) and self-control (goal maintenance). Four hypotheses were derived from Wojdylo- work craving theory and Kuhl- self-regulation theory: (H1) Work craving is associated with a combination of low self-regulation and high self-control. (H2) Work craving is associated with symptoms of psychological distress. (H3) Low self-regulation is associated with psychological distress symptoms. (H4) Work craving mediates the relationships between self-regulation deficits and psychological distress symptoms at high levels of self-control. Additionally, we aimed at supporting the discriminant validity of work craving with respect to work engagement by showing their different volitional underpinnings. Results of the two studies confirmed our hypotheses: whereas work craving was predicted by high self-control and low self-regulation and associated with higher psychological distress, work engagement was predicted by high self-regulation and high self-control and associated with lower symptoms of psychological distress. Furthermore, work styles mediated the relationship between volitional skills and symptoms of psychological distress. Based on these new insights, several suggestions for prevention and therapeutic interventions for work-addicted individuals are proposed.
The overall objective of this thesis was to gain a deeper understanding of the antecedents, processes, and manifestations of uniqueness-driven consumer behavior. To achieve this goal, five studies have been conducted in Germany and Switzerland with a total of 1048 participants across different demographic and socio-economic backgrounds. Two concepts were employed in all studies: Consumer need for uniqueness (CNFU) and general uniqueness perception (GUP). CNFU (Tian, Bearden, & Hunter, 2001), a mainly US"based consumer research concept, measures the individual need, and thus the motivation to acquire, use, and dispose consumer goods in order to develop a unique image. GUP, adapted from the two-component theory of individuality (Kampmeier, 2001), represents a global and direct measure of self-ascribed uniqueness. Study #1 looked at the interrelation of the uniqueness-driven concepts. Therefore, GUP and CNFU were employed in the study as potential psychological factors that influence and predict uniqueness-driven consumer behavior. Different behavioral measures were used: The newly developed possession of individualized products (POIP), the newly developed products for uniqueness display (PFUD), and the already established uniqueness-enhancing behaviors (UEB). Analyses showed that CNFU mediates the relationship between GUP and the behavioral measures in a German speaking setting. Thus, GUP (representing self-perception) was identified as the driver behind CNFU (representing motivation) and the actual consumer behavior. Study #2 examined further manifestations of uniqueness-driven consumer behavior. For this purpose, an extreme form of uniqueness-increasing behavior was researched: Tattooing. The influence of GUP and CNFU on tattooing behavior was investigated using a sample derived from a tattoo exhibition. To do so, a newly developed measure to determine the percentage of the body covered by tattoos was employed. It was revealed that individuals with higher GUP and CNFU levels indeed have a higher tattooing degree. Study #3 further explored the predictive possibilities and limitations of the GUP and CNFU concepts. On the one hand, study #3 specifically looked at the consumption of customized apparel products as mass customization is said to become the standard of the century (Piller & Müller, 2004). It was shown that individuals with higher CNFU levels not only purchased more customized apparel products in the last six months, but also spend more money on them. On the other hand, uniqueness-enhancing activities (UEA), such as travel to exotic places or extreme sports, were investigated by using a newly developed 30-item scale. It was revealed that CNFU partly mediates the GUP and UEA relationship, proving that CNFU indeed predicts a broad range of consumer behaviors and that GUP is the driver behind the need and the behavior. Study #4, entered a new terrain. In contrast to the previous three studies, it explored the so termed "passive" side of uniqueness-seeking in the consumer context. Individuals might feel unique because business companies treat them in a special way. Such a unique customer treatment (UCT) involves activities like customer service or customer relationship management. Study #4 investigated if individuals differ in their need for such a treatment. Hence, with the need for unique customer treatment (NFUCT) a new uniqueness-driven consumer need was introduced and its impact on customer loyalty examined. Analyses, for example, revealed that individuals with high NFUCT levels receiving a high unique customer treatment (UCT) showed the highest customer loyalty, whereas the lowest customer loyalty was found among those individuals with high NFUCT levels receiving a low unique customer treatment (UCT). Study #5 mainly examined the processes behind uniqueness-driven consumer behavior. Here, not only the psychological influences, but also situational influences were examined. This study investigated the impact of a non-personal "indirect" uniqueness manipulation on the consumption of customized apparel products by simultaneously controlling for the influence of GUP and CNFU. Therefore, two equal experimental groups were created. Afterwards, these groups either received an e-mail with a "pro-individualism" campaign or a "pro-collectivism" campaign especially developed for study #5. The conducted experiment revealed that, individuals receiving a "pro-individualism" poster campaign telling the participants that uniqueness is socially appropriate and desired were willing to spend more money on customization options compared to individuals receiving a "pro-collectivism" poster campaign. Hence, not only psychological antecedents such as GUP and CNFU influence uniqueness-driven consumer behavior, but also situational factors.
Software and interactive systems that adapt their behavior to the user are often referred to as Adaptive Systems. These systems infer the user's goals, knowledge or preferences by observing the user's actions. A synposis of 43 published studies demonstrated that only few of the existing systems are evaluated empirically. Most studies failed to show an advantage of the user model. A new framework is proposed that categorizes existing studies and defines an evaluation procedure which is able to uncover failures and maladaptations in the user model. It consists of four layers: evaluation of input data, evaluation of inference, evaluation of adaptation decision and evaluation of total interaction. Exemplary, the framework has been applied to the HTML-Tutor, an online-course that adapts to the learners' knowledge. Several empirical studies are described that test the accuracy of the user models, and explore the effects of adaptation to knowledge respectively prior knowledge. Generalization issues of the approach are discussed.
This study investigated correlative, factorial, and structural relationships between scores for ability emotional intelligence in the workplace (measured with the Geneva Emotional Competence Test), as well as fluid and crystallized abilities (measured with the Intelligence Structure Battery), carried out by a 188-participant student sample. Confirming existing research, recognition, understanding, and management of emotions were related primarily to crystallized ability tests measuring general knowledge, verbal fluency, and knowledge of word meaning. Meanwhile, emotion regulation was the least correlated with any other cognitive or emotional ability. In line with research on the trainability of emotional intelligence, these results may support the notion that emotional abilities are subject to acquired knowledge, where situational (i.e., workplace-specific) emotional intelligence may depend on accumulating relevant experiences.
In this thesis, in order to shed light on the biological function of the membrane-bound Glucocorticoid Receptor (mGR), proteomic changes induced by 15 min in vivo acute stress and by short in vitro activation of the mGR were analyzed in T-lymphocytes. The numerous overlaps between the two datasets suggest that the mGR mediates physiologically relevant actions and participates in the early stress response, triggering rapid early priming events that pave the way for the slower genomic GC activities. In addition, a new commercially available method with suitable sensitivity to detect the human mGR is reported and the transcriptional origin of this protein investigated. Our results indicates that specific GR-transcripts, containing exon 1C and 1D, are associated with the expression of this membrane isoform.
Advances in eye tracking technology have enabled the development of interactive experimental setups to study social attention. Since these setups differ substantially from the eye tracker manufacturer’s test conditions, validation is essential with regard to the quality of gaze data and other factors potentially threatening the validity of this signal. In this study, we evaluated the impact of accuracy and areas of interest (AOIs) size on the classification of simulated gaze (fixation) data. We defined AOIs of different sizes using the Limited-Radius Voronoi-Tessellation (LRVT) method, and simulated gaze data for facial target points with varying accuracy. As hypothesized, we found that accuracy and AOI size had strong effects on gaze classification. In addition, these effects were not independent and differed in falsely classified gaze inside AOIs (Type I errors; false alarms) and falsely classified gaze outside the predefined AOIs (Type II errors; misses). Our results indicate that smaller AOIs generally minimize false classifications as long as accuracy is good enough. For studies with lower accuracy, Type II errors can still be compensated to some extent by using larger AOIs, but at the cost of more probable Type I errors. Proper estimation of accuracy is therefore essential for making informed decisions regarding the size of AOIs in eye tracking research.
Evaluation of an eye tracking setup for studying visual attention in face-to-face conversations
(2021)
Many eye tracking studies use facial stimuli presented on a display to investigate attentional processing of social stimuli. To introduce a more realistic approach that allows interaction between two real people, we evaluated a new eye tracking setup in three independent studies in terms of data quality, short-term reliability and feasibility. Study 1 measured the robustness, precision and accuracy for calibration stimuli compared to a classical display-based setup. Study 2 used the identical measures with an independent study sample to compare the data quality for a photograph of a face (2D) and the face of the real person (3D). Study 3 evaluated data quality over the course of a real face-to-face conversation and examined the gaze behavior on the facial features of the conversation partner. Study 1 provides evidence that quality indices for the scene-based setup were comparable to those of a classical display-based setup. Average accuracy was better than 0.4° visual angle. Study 2 demonstrates that eye tracking quality is sufficient for 3D stimuli and robust against short interruptions without re-calibration. Study 3 confirms the long-term stability of tracking accuracy during a face-to-face interaction and demonstrates typical gaze patterns for facial features. Thus, the eye tracking setup presented here seems feasible for studying gaze behavior in dyadic face-to-face interactions. Eye tracking data obtained with this setup achieves an accuracy that is sufficient for investigating behavior such as eye contact in social interactions in a range of populations including clinical conditions, such as autism spectrum and social phobia.
Cortisol exhibits typical ultradian and circadian rhythm and disturbances in its secretory pattern have been described in stress-related pathology. The aim of this thesis was to dissect the underlying structure of cortisol pulsatility and to develop tools to investigate the effects of this pulsatility on immune cell trafficking and the responsiveness of the neuroendocrine system and GR target genes to stress. Deconvolution modeling was set up as a tool for investigation of the pulsatile secretion underlying the ultradian cortisol rhythm. This further allowed us to investigate the role of the single cortisol pulses on the immune cell trafficking and the role of induced cortisol pulses on the kinetics of expression of GR target genes. The development of these three tools, would allow to induce and investigate in future the significance of single cortisol pulses for health and disease.
Salivary alpha-amylase (sAA) influences the perception of taste and texture, features both relevant in acquiring food liking and, with time, food preference. However, no studies have yet investigated the relationship between basal activity levels of sAA and food preference. We collected saliva from 57 volunteers (63% women) who we assessed in terms of their preference for different food items. These items were grouped into four categories according to their nutritional properties: high in starch, high in sugar, high glycaemic index, and high glycaemic load. Anthropometric markers of cardiovascular risk were also calculated. Our findings suggest that sAA influences food
preference and body composition in women. Regression analysis showed that basal sAA activity is inversely associated with subjective but not self-reported behavioural preference for foods high in sugar. Additionally, sAA and subjective preference are associated with anthropometric markers of cardiovascular risk. We believe that this pilot study points to this enzyme as an interesting candidate to consider among the physiological factors that modulate eating behaviour.
Dysfunctional eating behavior is a major risk factor for developing all sorts of eating disorders. Food craving is a concept that may help to understand better why and how these and other eating disorders become chronic conditions through non homeastatically-driven mechanisms. As obesity affects people worldwide, cultural differences must be acknowledged to apply proper therapeutic strategies. In this work, we adapted the Food Craving Inventory (FCI) to the German population. We performed a factor analysis of an adaptation of the original FCI in a sample of 326 men and women. We could replicate the factor structure of the FCI on a German population.rnThe factor extraction procedure produced a factor solution that reproduces the fourfactors described in the original inventory, the FCI. Our instrument presents high internal consistency, as well as a significant correlation with measures of convergent and discriminant validity. The FCI-Deutsch (FCI-DE) is a valid instrument to assess craving for particular foods in Germany, and it could, therefore, prove useful in the clinical and research practice in the field of obesity and eating behaviors.
Cortisol is a stress hormone that acts on the central nervous system in order to support adaptation and time-adjusted coping processes. Whereas previous research has focused on slow emerging, genomic effects of cortisol likely mediated by protein synthesis, there is only limited knowledge about rapid, non-genomic cortisol effects on in vivo neuronal cell activity in humans. Three independent placebo-controlled studies in healthy men were conducted to test effects of 4 mg cortisol on central nervous system activity, occurring within 15 minutes after intravenous administration. Two of the studies (N = 26; N = 9) used continuous arterial spin labeling as a magnetic resonance imaging sequence, and found rapid bilateral thalamic perfusion decrements. The third study (N = 14) revealed rapid cortisol-induced changes in global signal strength and map complexity of the electroencephalogram. The observed changes in neuronal functioning suggest that cortisol may act on the thalamic relay of non-relevant background as well as on task specific sensory information in order to facilitate the adaptation to stress challenges. In conclusion, these results are the first to coherently suggest that a physiologically plausible amount of cortisol profoundly affects functioning and perfusion of the human CNS in vivo by a rapid, non-genomic mechanism.
During the last decade, anatomic and physiological neuroscience research has yielded extensive information on the physiological regulators of short-term satiety, visceral and interoceptive sensation. Distinct neural circuits regulate the elements of food ingestion physiologically. The general aim of the current studies is to elucidate the peripheral neural pathways to the brain in healthy subjects to establish the groundwork for the study of the pathophysiology of bulimia nervosa (BN). We aimed to define the central activation pattern during non-nutritive gastric distension in humans, and aimed to define the cognitive responses to this mechanical gastric distension. We estimated regional cerebral blood flow with 15O-water positron emission tomography during intragastric balloon inflation and deflation in 18 healthy young women of normal weight. The contrast between inflated minus deflated in the exploratory analysis revealed activation in more than 20 brain regions. The analysis confirmed several well known areas in the central nervous system that contribute to visceral processing: the inferior frontal cortex, representing a zone of convergence for food related stimuli; the insula and operculum referred to as "visceral cortex"; the anterior cingulate gyrus (and insula), processing affective information; and the brainstem, a site of vagal relay for visceral afferent stimuli. Brain activation in the left ventrolateral prefrontal cortex was reproducible. This area is well known for higher cognitive processing, especially reward-related stimuli. The ventrolateral prefrontal cortex with the insular regions may provide a link between the affective and rewarding components of eating and disordered eating as observed in BN and binge-eating obesity. Gastric distension caused a significant rapid, reversible, and reproducible increase in the feelings of fullness, sleepiness, and gastric discomfort as well as a significant rapid, reversible, and reproducible decrease in the feeling of hunger. We showed that mechanical activation of the neurocircuitry involved in meal termination led to the described phenomena. The current brain activation studies of non-painful, proximal gastric distension could provide groundwork in the field of abnormal eating behavior by suggesting a link between visceral sensation and abnormal eating patterns. A potential treatment for disordered eating and obesity could alter the conscious and unconscious perception and interoceptive awareness of gastric distension contributing to meal termination.
The human brain is characterised by two apparently symmetrical cerebral hemispheres. However, the functions attributed to each half of the brain are very distinct with a relative specialisation of the left hemisphere for language processing. Most laterality research has been performed on a behavioural level, using techniques such as visual half-field presentation. The visual half-field technique involves the presentation of stimuli in the left or right visual field for a very short time (about 200 ms). During the presentation of lateralized stimuli, the gaze of the participants is fixated on a centrally presented fixation cross. This technique takes advantage of the anatomy of the visual pathway as the temporal hemiretinae project ipsilateral, while the nasal hemiretinae project contralateral. Thus, stimuli presented in the left or right visual field are initially processed in the contralateral hemisphere. Language organisation can also be directly investigated using functional magnetic resonance imaging (fMRI). Both behavioural and neuroimaging studies showed that about 95% of right-handed men have a left hemispheric specialisation for language. In contrast, data on language organisation in women are ambiguous. It is supposed that this ambivalent picture might be associated with changes in gonadal steroid levels in blood during the menstrual cycle. However, gonadal steroid effects are complex and their role in functional cerebral lateralization is still open to discussion. The aim of this PhD project was to investigate, using fMRI: (1) the processing of linguistic information initially received in the specialised, non-specialised or both hemispheres; (2) linking the associated brain activation pattern with progesterone levels during the menstrual cycle. Firstly, brain activation was measured in 16 right-handed, healthy males during processing of different components of language (orthography, phonology and semantics) after reception in the left, right or both hemispheres. Secondly, to investigate changes in language organisation during the menstrual cycle, we conducted an event-related fMRI study during semantic and phonological processing also using visual half-field and central presentation of linguistic stimuli. Our results revealed higher BOLD signal intensity change in the visual cortex contralateral to the visual field of stimulus presentation compared to the ipsilateral visual cortex reflecting the crossing of visual pathways. We also found support for the hypothesis that the superiority of word recognition in the left VWFA is the result of a reduced activity in the right VWFA under left hemispheric control. Further, linguistic information received in the subdominant RH, is interhemispheric transferred to the left hemisphere for phonological processing. Semantic processing in contrast occurs in the specialised and in the non-specialised hemisphere. For the group of women, data analysis revealed that during semantic processing, salivary progesterone levels correlated positively with brain activity of the left superior frontal gyrus, left middle and inferior occipital gyri and bilateral fusiform gyrus. In contrast, the brain activation pattern for phonological processing did not change significantly across the menstrual cycle. In conclusion, the effect of serum progesterone levels on brain activity is task and region specific.
Background: We evaluated depression and social isolation assessed at time of waitlisting as predictors of survival in heart transplant (HTx) recipients. Methods and Results: Between 2005 and 2006, 318 adult HTx candidates were enrolled in the Waiting for a New Heart Study, and 164 received transplantation. Patients were followed until February 2013. Psychosocial characteristics were assessed by questionnaires. Eurotransplant provided medical data at waitlisting, transplantation dates, and donor characteristics; hospitals reported medical data at HTx and date of death after HTx. During a median followâ€up of 70 months (<1"93 months postâ€HTx), 56 (38%) of 148 transplanted patients with complete data died. Depression scores were unrelated to social isolation, and neither correlated with disease severity. Higher depression scores increased the risk of dying (hazard ratio=1.07, 95% confidence interval, 1.01, 1.15, P=0.032), which was moderated by social isolation scores (significant interaction term; hazard ratio = 0.985, 95% confidence interval, 0.973, 0.998; P=0.022). These findings were maintained in multivariate models controlling for covariates (P values 0.020"0.039). Actuarial 1â€year/5â€year survival was best for patients with low depression who were not socially isolated at waitlisting (86% after 1 year, 79% after 5 years). Survival of those who were either depressed, or socially isolated or both, was lower, especially 5 years posttransplant (56%, 60%, and 62%, respectively). Conclusions: Low depression in conjunction with social integration at time of waitlisting is related to enhanced chances for survival after HTx. Both factors should be considered for inclusion in standardized assessments and interventions for HTx candidates. We evaluated depression and social isolation assessed at time of waitlisting as predictors of survival in heart transplant (HTx) recipients.\r\n\r\nMethods and Results: Between 2005 and 2006, 318 adult HTx candidates were enrolled in the Waiting for a New Heart Study, and 164 received transplantation. Patients were followed until February 2013. Psychosocial characteristics were assessed by questionnaires. Eurotransplant provided medical data at waitlisting, transplantation dates, and donor characteristics; hospitals reported medical data at HTx and date of death after HTx. During a median followâ€up of 70 months (<1"93 months postâ€HTx), 56 (38%) of 148 transplanted patients with complete data died. Depression scores were unrelated to social isolation, and neither correlated with disease severity. Higher depression scores increased the risk of dying (hazard ratio=1.07, 95% confidence interval, 1.01, 1.15, P=0.032), which was moderated by social isolation scores (significant interaction term; hazard ratio = 0.985, 95% confidence interval, 0.973, 0.998; P=0.022). These findings were maintained in multivariate models controlling for covariates (P values 0.020"0.039). Actuarial 1â€year/5â€year survival was best for patients with low depression who were not socially isolated at waitlisting (86% after 1 year, 79% after 5 years). Survival of those who were either depressed, or socially isolated or both, was lower, especially 5 years posttransplant (56%, 60%, and 62%, respectively).
This thesis presents a study of the visual change detection mechanism. This mechanism is thought to be responsible for the detection of sudden and unexpected changes in our visual environment. As the brain is a capacity limited system and has to deal with a continuous stream of information from its surroundings only a part of the vast amount of information can be completely processed and be brought to conscious awareness. This information, which passes through attentional filters, is used for goal-directed behaviour. Therefore, the change detection mechanism is a very useful aid to cope with important information which is outside the focus of our attention. rnIt is thought that a neural memory trace of repetitive visual information is stored. Each new information input is compared to this existing memory trace by a so-called change or mismatch detection system. Following a sudden change, the comparison process leads to a mismatch and the detection system elicits a warning signal, to which an orienting response can follow. This involves a change in the focus of attention towards this sudden environmental change which can then be evaluated for potential danger and allows for a behavioural adaptation to the new situation. rnTo this purpose a paradigm was developed combining a 2-choice response time task with in the background a mismatch detection task of which the subjects were not aware. This paradigm was implemented in an ERP and an fMRI study and was used to study the the change detection mechanism and its relationship with impulsivity.rnIn previous studies a change detection system for auditory information had already been established. As the brain is a very efficient system it was thought to be unlikely that this change detection system is only available for the processing of auditory information. rnIndeed, a modality specific mismatch response at the sensory specific occipital cortex and a more general response at the frontocentral midline, both resembling the components shown in auditory research, were found in the ERP study.rnAdditionally, magnetic resonance imaging revealed a possible functional network of regions, which responded specifically to the processing of a deviant. These regions included the occipital gyrus, premotor cortex, inferior frontal cortex, thalamas, insula, and parts of the cingular cortex. rnThe relationship between impulsivity measures and visual change detection was established in an additional study. More impulsive subjects showed less detection of deviant stimuli, which was most likely due to too fast and imprecise information processing.rnIn summary it can be said, that the work presented in this thesis demonstrates that visual mismatch negativity was established, a number of regions could be associated with change detection and additionally the relevance of change detection in information processing was shown.rn
At any given moment, our senses are assaulted with a flood of information from the environment around us. We need to pick our way through all this information in order to be able to effectively respond to that what is relevant to us. In most cases we are usually able to select information relevant to our intentions from what is not relevant. However, what happens to the information that is not relevant to us? Is this irrelevant information completely ignored so that it does not affect our actions? The literature suggests that even though we mayrnignore an irrelevant stimulus, it may still interfere with our actions. One of the ways in which irrelevant stimuli can affect actions is by retrieving a response with which it was associated. An irrelevant stimulus that is presented in close temporal contiguity with a relevant stimulus can be associated with the response made to the relevant stimulus " an observation termed distractor-response binding (Rothermund, Wentura, & De Houwer, 2005). The studies presented in this work take a closer look at such distractor-response bindings, and therncircumstances in which they occur. Specifically, the study reported in chapter 6 examined whether only an exact repetition of the distractor can retrieve the response with which it was associated, or whether even similar distractors may cause retrieval. The results suggested that even repeating a similar distractor caused retrieval, albeit less than an exact repetition. In chapter 7, the existence of bindings between a distractor and a response were tested beyond arnperceptual level, to see whether they exist at an (abstract) conceptual level. Similar to perceptual repetition, distractor-based retrieval of the response was observed for the repetition of concepts. The study reported in chapter 8 of this work examined the influence of attention on the feature-response binding of irrelevant features. The results pointed towards a stronger binding effects when attention was directed towards the irrelevant feature compared to whenrnit was not. The study in chapter 9 presented here looked at the processes underlying distractor-based retrieval and distractor inhibition. The data suggest that motor processes underlie distractor-based retrieval and cognitive process underlie distractor inhibition. Finally, the findings of all four studies are also discussed in the context of learning.
The search for relevant determinants of knowledge acquisition has a long tradition in educational research, with systematic analyses having started over a century ago. To date, a variety of relevant environmental and learner-related characteristics have been identified, providing a wide body of empirical evidence. However, there are still some gaps in the literature, which are highlighted in the current dissertation. The dissertation includes two meta-analyses summarizing the evidence on the effectiveness of electrical brain stimulation and the effects of prior knowledge on later learning outcomes and one empirical study employing latent profile transition analysis to investigate the changes in conceptual knowledge over time. The results from the three studies demonstrate how learning outcomes can be advanced by input from the environment and that they are highly related to the students" level of prior knowledge. It is concluded that the effects of environmental and learner-related variables impact both the biological and cognitive processes underlying knowledge acquisition. Based on the findings from the three studies, methodological and practical implications are provided, followed by an outline of four recommendations for future research on knowledge acquisition.
In addition to the well-recognised effects of both, genes and adult environment, it is now broadly accepted that adverse conditions during pregnancy contribute to the development of mental and somatic disorders in the offspring, such as cardiovascular disorders, endocrinological disorders, metabolic disorders, schizophrenia, anxious and depressive behaviour and attention deficit hyperactivity disorder (ADHD). Early life events may have long lasting impact on tissue structure and function and these effects appear to underlie the developmental origins of vulnerability to chronic diseases. The assumption that prenatal adversity, such as maternal emotional states during pregnancy, may have adverse effects on the developing infant is not new. Accordant references can be found in an ancient Indian text (ca. 1050 before Christ), in biblical texts and in documents originating during the Middle Ages. Even Hippocrates stated possible effects of maternal emotional states on the developing fetus. Since the mid-1950s, research examining the effects of maternal psychosocial stress during pregnancy appeared in the literature. Extensive research in this field has been conducted since the early 1990s. Thus, the relationship between early life events and long-term health outcomes was already postulated over 20 years ago. David Barker and colleagues demonstrated that children of lower birth weight - which represents a crude marker of an adverse intrauterine environment - were at increased risk of high blood pressure, cardiovascular disorders, and type-2 diabetes later in life. These provocative findings led to a large amount of subsequent research, initially focussing on the role of undernutrition in determining fetal outcomes. The phenomenon of prenatal influences that determine in part the risk of suffering from chronic disease later in life has been named the "fetal origins of health and disease" paradigm. The concept of "prenatal programming" has now been extended to many other domains, such as the effects of prenatal maternal stress, prenatal tobacco exposure, alcohol intake, medication, toxins, as well as maternal infection and diseases. During the process of prenatal programming, environmental agents are transmitted across the placenta and act on specific fetal tissues during sensitive periods of development. Thus, developmental trajectories are changed and the organisation and function of tissue structure and organ system is altered. The biological purpose of those "early life programming" may consist in evolutionary advantages. The offspring adapts its development to the expected extrauterine environment which is forecast by the clues available during fetal life. If the fetus receives signals of a challenging environment, e.g. due to maternal stress hormones or maternal undernutrition, its survival may be promoted due to developmental adaptation processes. However, if the expected environment does not match with the real environment, maladapation and later disease risk may result. For example, a possible indicator of a "response ready" trait, such as hyperactivity/inattention may have been advantageous in an adverse ancient environment. However, it is of disadvantage when the postnatal environment demands oppositional skills, such as attention and concentration " e.g. in the classroom, at school, to achieve academic success. Borderline personality disorder (BPD) is a prevalent psychiatric disorder, characterized by impulsivity, affective instability, dysfunctional interpersonal relationships and identity disturbance. Although many studies report different risk factors, the exact etiologic mechanisms are not yet understood. In addition to the well-recognised effects of genetic components and adverse childhood experiences, BPD may potentially be co-determined by further environmental influences, acting very early in life: during pre- and perinatal period. There are several hints that may suggest possible prenatal programming processes in BPD. For example, patients with BPD are characterized by elevated stress sensitivity and reactivity and dysfunctions of the neuroendocrine stress system, such as the hypothalamic pituitary adrenal (HPA) axis. Furthermore, patients with BPD show a broad range of somatic comorbidities " especially those disorders for which prenatal programming processes have been described. During infancy and childhood, BPD patients already show behavioural and emotional abnormalities as well as pronounced temperamental traits, such as impulsivity, emotional dysregulation and inattention that may potentially be co-determined by prenatal programming processes. Such temperamental traits - similar to those, seen in patients with ADHD - have been described to be associated with low birthweight which indicates a suboptimal intrauterine environment. Moreover, the functional and structural alterations in the central nervous system (CNS) in patients with BPD might also be mediated in part by prenatal agents, such as prenatal tobacco exposure. Prenatal adversity may thus constitute a further, additional component in the multifactorial genesis of BPD. The association between BPD and prenatal risk factors has not yet been studied in such detail. We are not aware of any further study that assessed pre- and perinatal risk factors, such as maternal psychoscocial stress, smoking, alcohol intake, obstetric complications and lack of breastfeeding in patients with BPD.
Objective: Attunement is a novel measure of nonverbal synchrony reflecting the duration of the present moment shared by two interaction partners. This study examined its association with early change in outpatient psychotherapy.
Methods: Automated video analysis based on motion energy analysis (MEA) and cross-correlation of the movement time-series of patient and therapist was conducted to calculate movement synchrony for N = 161 outpatients. Movement-based attunement was defined as the range of connected time lags with significant synchrony. Latent change classes in the HSCL-11 were identified with growth mixture modeling (GMM) and predicted by pre-treatment covariates and attunement using multilevel multinomial regression.
Results: GMM identified four latent classes: high impairment, no change (Class 1); high impairment, early response (Class 2); moderate impairment (Class 3); and low impairment (Class 4). Class 2 showed the strongest attunement, the largest early response, and the best outcome. Stronger attunement was associated with a higher likelihood of membership in Class 2 (b = 0.313, p = .007), Class 3 (b = 0.251, p = .033), and Class 4 (b = 0.275, p = .043) compared to Class 1. For highly impaired patients, the probability of no early change (Class 1) decreased and the probability of early response (Class 2) increased as a function of attunement.
Conclusions: Among patients with high impairment, stronger patient-therapist attunement was associated with early response, which predicted a better treatment outcome. Video-based assessment of attunement might provide new information for therapists not available from self-report questionnaires and support therapists in their clinical decision-making.
Memory consists of multiple anatomically and functionally distinct systems. Animal studies suggest that stress modulates multiple memory systems in a manner that favors nucleus caudatus-based stimulus-response learning at the expense of hippocampus-based spatial learning. The present work aimed (i) to translate these findings to humans, (ii) to determine the involvement of the stress hormone cortisol in this effect, and (iii) to assess whether the use of stimulus-response and spatial strategies is a long lasting person characteristic. To address these issues we developed a new paradigm that differentiates the use of spatial and stimulus-response learning in humans. Our findings indicate that (i) psychosocial stress (Trier Social Stress Test) modulates the use of spatial and stimulus-response learning in humans, (ii) cortisol plays a key role in this modulatory effect of stress, and (iii) the use of spatial and stimulus-response learning is affected by situational rather than long lasting person factors.
The present thesis addresses the validity of Binge Eating Disorder (BED) as well as underlying mechanisms of BED from three different angles. Three studies provide data discriminating obesity with BED from obesity without BED. Study 1 demonstrates differences between obese individuals with and without BED regarding eating in the natural environment, psychiatric comorbidity, negative affect as well as self reported tendencies in eating behavior. Evidence for possible psychological mechanisms explaining increased intake of BED individuals in the natural environment was given by analyzing associations of negative affect, emotional eating, restrained eating and caloric intake in obese BED compared to NBED controls. Study 2 demonstrated stress-induced changes in the eating behavior of obese individuals with BED. The impact of a psychosocial stressor, the Trier Social Stress Test (TSST, Kirschbaum, Pirke, &amp;amp; Hellhammer, 1993), on behavioral patterns of eating behavior in laboratory was investigated. Special attention was given to stress-induced changes in variables that reflect mechanisms of appetite regulation in obese BED individuals compared to controls. To further explore by which mechanisms stress might trigger binge eating, study 3 investigated differences in stress-induced cortisol secretion after a socially evaluated cold pressure test (SECPT, Schwabe, Haddad, &amp;amp; Schachinger, 2008) in obese BED as compared to obese NBED individuals.
Interoception - the perception of bodily processes - plays a crucial role in the subjective experience of emotion, consciousness and symptom genesis. As an alternative to interoceptive paradigms that depend on the participants" active cooperation, five studies are presented to show that startle methodology may be employed to study visceral afferent processing. Study 1 (38 volunteers) showed that startle responses to acoustic stimuli of 105 dB(A) intensity were smaller when elicited during the cardiac systole (R-wave +230 ms) as compared to the diastole (R +530 ms). In Study 2, 31 diabetic patients were divided into two groups with normal or diminished (< 6 ms/mmHg) baroreflex sensitivity (BRS) of heart rate control. Patients with normal BRS showed a startle inhibition during the cardiac systole as was found for healthy volunteers. Diabetic patients with diminished BRS did not show this pattern. Because diminished BRS is an indicator of impaired baro-afferent signal transmission, we concluded that cardiac modulation of startle is associated with intact arterial baro-afferent feedback. Thus, pre-attentive startle methodology is feasible to study visceral afferent processing. rnVisceral- and baro-afferent information has been found to be mainly processed in the right hemisphere. To explore whether cardiac modulation of startle eye blink is lateralized as well, in Study 3, 37 healthy volunteers received 160 unilateral acoustic startle stimuli presented to both ears, one at a time (R +0, 100, 230, 530 ms). Startle response magnitude was only diminished at R +230 ms and for left-ear presentation. This lateralization effect in the cardiac modulation of startle eye blink may reflect the previously described advantages of right-hemispheric brain structures in relaying viscero- and baro-afferent signal transmission. rnThis lateralization effect implies that higher cognitive processes may also play a role in the cardiac modulation of startle. To address this question, in Study 4, 25 volunteers responded first by 'fast as possible' button pushes (reaction time, RT), and second, rated perceived intensity of 60 acoustic startle stimuli (85, 95, or 105 dB; R +230, 530 ms). RT was divided into evaluation and motor response time. Increasing stimulus intensity enhanced startle eye blink, intensity ratings, and RT components. Eye blinks and intensity judgments were lower when startle was elicited at a latency of R +230 ms, but RT components were differentially affected. It is concluded that the cardiac cycle affects the attentive processing of acoustic startle stimuli. rnBeside the arterial baroreceptors, the cardiopulmonary baroreceptors represent another important system of cardiovascular perception that may have similar effects on startle responsiveness. To clarify this issue, in Study 5, Lower Body Negative Pressure at gradients of 0, -10, -20, and -30 mmHg was applied to unload cardiopulmonary baroreceptors in 12 healthy males, while acoustic startle stimuli were presented (R +230, 530 ms). Unloading of cardiopulmonary baroreceptors increased startle eye blink responsiveness. Furthermore, the effect of relative loading/unloading of arterial baroreceptors on startle eye blink responsiveness was replicated. These results demonstrate that the loading status of cardiopulmonary baroreceptors also has an impact on brainstem-based CNS processes. rnThus, the cardiac modulation of acoustic startle is feasible to reflect baro-afferent signal transmission of multiple neural sources, it represents a pre-attentive method that is independent of active cooperation, but its modulatory effects also reach higher cognitive, attentive processes.rn
In this psycho-neuro-endocrine study the molecular basis of different variants of steroid receptors as well as highly conserved non steroidal receptors was investigated. These nuclear receptors (NRs) are important key regulators of a wide variety of different physiological and pathophysiological challenges ranging from inflammation and stress to complex behaviour and disease. NRs control gene transcription in a ligand dependent manner and are embedded in the huge interaction network of the neuroendocrine and immune system. Two receptors, the glucocorticoid receptor (GR) and the chicken ovalbumin upstream promoter-transcription factorII (Coup-TFII), both expressed in the immune and nervous system, were investigated regarding possible splice variants and their implication in the control of gene transcription. Both NRs are known to interact and modulate each other- target gene regulation. This study could be shown that both NRs have different splice variants that are expressed in a tissue specific manner. The different 5-´alternative transcript variants of the human GR were in silico identified in other species and evidence for a highly conserved and tightly controlled function was provided. Investigations of the N-terminal transactivation domain of the GR showed a deletion suggesting an altered glucocorticoid-dependent transactivation profile. The newly identified alternative transcript variant of Coup-TFII leads to a DNA binding deficient Coup-TFII isoform that is highly expressed in the brain. This Coup-TFII isoform alters Coup-TFII target gene expression and is suggested to interact with GR via its ligand binding domain resulting in an impaired GR target gene regulation in the nervous system. In this thesis it was demonstrated that NR variants are important for the understanding of the enormous regulatory potential of this receptor family and have to be taken into account for the development of therapeutic strategies for complex diseases such as stress related and neurodegenerative disorders.
Primary focal hyperhidrosis (PFH, OMIM %144110) is a genetically influenced condition characterised by excessive sweating. Prevalence varies between 1.0–6.1% in the general population, dependent on ethnicity. The aetiology of PFH remains unclear but an autosomal dominant mode of inheritance, incomplete penetrance and variable phenotypes have been reported. In our study, nine pedigrees (50 affected, 53 non-affected individuals) were included. Clinical characterisation was performed at the German Hyperhidrosis Centre, Munich, by using physiological and psychological questionnaires. Genome-wide parametric linkage analysis with GeneHunter was performed based on the Illumina genome-wide SNP arrays. Haplotypes were constructed using easyLINKAGE and visualised via HaploPainter. Whole-exome sequencing (WES) with 100x coverage in 31 selected members (24 affected, 7 non-affected) from our pedigrees was achieved by next generation sequencing. We identified four genome-wide significant loci, 1q41-1q42.3, 2p14-2p13.3, 2q21.2-2q23.3 and 15q26.3-15q26.3 for PFH. Three pedigrees map to a shared locus at 2q21.2-2q23.3, with a genome-wide significant LOD score of 3.45. The chromosomal region identified here overlaps with a locus at chromosome 2q22.1-2q31.1 reported previously. Three families support 1q41-1q42.3 (LOD = 3.69), two families share a region identical by descent at 2p14-2p13.3 (LOD = 3.15) and another two families at 15q26.3 (LOD = 3.01). Thus, our results point to considerable genetic heterogeneity. WES did not reveal any causative variants, suggesting that variants or mutations located outside the coding regions might be involved in the molecular pathogenesis of PFH. We suggest a strategy based on whole-genome or targeted next generation sequencing to identify causative genes or variants for PFH.
The Role of Dopamine and Acetylcholine as Modulators of Selective Attention and Response Speed
(2015)
The principles of top-down and bottom-up processing are essential to cognitive psychology. At their broadest, most general definition, they denote that processing can be driven either by the salience of the stimulus input or by individual goals and strategies. Selective top-down attention, specifically, consists in the deliberate prioritizing of stimuli that are deemed goal-relevant, while selective bottom-up attention relies on the automatic allocation of attention to salient stimuli (Connor, Egeth, & Yantis, 2004; Schneider, Schote, Meyer, & Frings, 2014). Variations within neurotransmitter systems can modulate cognitive performance in a domain-specific fashion (Greenwood, Fossella, & Parasuraman, 2005). Noudoost and Moore (2011a) proposed that the influence of the dopaminergic neurotransmitter system on selective top-down attention might be greater than the influence of this system on selective bottom-up attention; likewise, they assumed that the cholinergic neurotransmitter system might be more important for selective bottom-up than top-down attention. To test this hypothesis, naturally occurring variations within the two neurotransmitter systems were assessed. Five polymorphisms were selected; two of the dopaminergic system (the COMT Val158Met polymorphism and the DAT1 polymorphism) and three of the cholinergic system (the CHRNA4 rs1044396 polymorphism, the CHRNA5 rs3841324 polymorphism, and the CHRNA5 rs16969968 polymorphism). It was tested whether these polymorphisms modulated the performance in tasks of selective top-down attention (a Stroop task and a Negative priming task) and in a task of selective bottom-up attention (a Posner-Cuing task). Indeed, the dopaminergic polymorphisms influenced selective top-down attention, but exerted no effects on bottom-up attention. This aligned with the hypothesis proposed by Noudoost and Moore (2011a). In contrast, the cholinergic polymorphisms were not found to modulate selective bottom-up attention. The three cholinergic polymorphisms, however, affected the general response speed in the Stroop task, Negative priming task, and Posner-Cuing task (irrespective of attentional processing). In sum, the findings of this study provide strong indications that the dopaminergic system modulates selective top-down attention, while the cholinergic system is highly relevant for the general speed of information processing.
Academic self-concept (ASC) is comprised of individual perceptions of one- own academic ability. In a cross-sectional quasi-representative sample of 3,779 German elementary school children in grades 1 to 4, we investigated (a) the structure of ASC, (b) ASC profile formation, an aspect of differentiation that is reflected in lower correlations between domain-specific ASCs with increasing grade level, (c) the impact of (internal) dimensional comparisons of one- own ability in different school subjects for profile formation of ASC, and (d) the role played by differences in school grades between subjects for these dimensional comparisons. The nested Marsh/Shavelson model, with general ASC at the apex and math, writing, and reading ASC as specific factors nested under general ASC fitted the data at all grade levels. A first-order factor model with math, writing, reading, and general ASCs as correlated factors provided a good fit, too. ASC profile formation became apparent during the first two to three years of school. Dimensional comparisons across subjects contributed to ASC profile formation. School grades enhanced these comparisons, especially when achievement profiles were uneven. In part, findings depended on the assumed structural model of ASCs. Implications for further research are discussed with special regard to factors influencing and moderating dimensional comparisons.
Fostering positive and realistic self-concepts of individuals is a major goal in education worldwide (Trautwein & Möller, 2016). Individuals spend most of their childhood and adolescence in school. Thus, schools are important contexts for individuals to develop positive self-perceptions such as self-concepts. In order to enhance positive self-concepts in educational settings and in general, it is indispensable to have a comprehensive knowledge about the development and structure of self-concepts and their determinants. To date, extensive empirical and theoretical work on antecedents and change processes of self-concept has been conducted. However, several research gaps still exist, and several of these are the focus of the present dissertation. Specifically, these research gaps encompass (a) the development of multiple self-concepts from multiple perspectives regarding stability and change, (b) the direction of longitudinal interplay between self-concept facets over the entire time period from childhood to late adolescence, and (c) the evidence that a recently developed structural model of academic self-concept (nested Marsh/Shavelson model [Brunner et al., 2010]) fits the data in elementary school students, (d) the investigation of structural changes in academic self-concept profile formation within this model, (e) the investigation of dimensional comparison processes as determinants of academic self-concept profile formation in elementary school students within the internal/external frame of reference model (I/E model; Marsh, 1986), (f) the test of moderating variables for dimensional comparison processes in elementary school, (g) the test of the key assumptions of the I/E model that effects of dimensional comparisons depend to a large degree on the existence of achievement differences between subjects, and (h) the generalizability of the findings regarding the I/E model over different statistical analytic methods. Thus, the aim of the present dissertation is to contribute to close these gaps with three studies. Thereby, data from German students enrolled in elementary school to secondary school education were gathered in three projects comprising the developmental time span from childhood to adolescence (ages 6 to 20). Three vital self-concept areas in childhood and adolescence were in-vestigated: general self-concept (i.e., self-esteem), academic self-concepts (general, math, reading, writing, native language), and social self-concepts (of acceptance and assertion). In all studies, data were analyzed within a latent variable framework. Findings are discussed with respect to the research aims of acquiring more comprehensive knowledge on the structure and development of significant self-concept in childhood and adolescence and their determinants. In addition, theoretical and practical implications derived from the findings of the present studies are outlined. Strengths and limitations of the present dissertation are discussed. Finally, an outlook for future research on self-concepts is given.
Fast and Slow Effects of Cortisol on Several Functions of the Central Nervous System in Humans
(2014)
Cortisol is one of the key substances released during stress to restore homeostasis. Our knowledge of the impact of this glucocorticoid on cognition and behavior in humans is, however, still limited. Two modes of action of cortisol are known, a rapid, nongenomic and a slow, genomic mode. Both mechanisms appear to be involved in mediating the various effects of stress on cognition. Here, three experiments are presented that investigated fast and slow effects of cortisol on several functions of the human brain. The first experiment investigated the interaction between insulin and slow, genomic cortisol effects on resting regional cerebral blood flow (rCBF) in 48 young men. A bilateral, locally distinct increase in rCBF in the insular cortex was observed 37 to 58 minutes after intranasal insulin admission. Cortisol did not influence rCBF, neither alone nor in interaction with insulin. This finding suggests that cortisol does not influence resting cerebral blood flow within a genomic timeframe. The second experiment examined fast cortisol effects on memory retrieval. 40 participants (20 of them female) learned associations between neutral male faces and social descriptions and were tested for recall one week later. Cortisol administered intravenously 8 minutes before retrieval influenced recall performance in an inverted U-shaped dose-response relationship. This study demonstrates a rapid, presumably nongenomic cortisol effect on memory retrieval in humans. The third experiment studied rapid cortisol effects on early multisensory integration. 24 male participants were tested twice in a focused cross-modal choice reaction time paradigm, once after cortisol and once after placebo infusion. Cortisol acutely enhanced the integration of visual targets and startling auditory distractors, when both stimuli appeared in the same sensory hemi-field. The rapidity of effect onset strongly suggests that cortisol changes multisensory integration by a nongenomic mechanism. The work presented in this thesis highlights the essential role of cortisol as a fast acting agent during the stress response. Both the second and the third experiment provide new evidence of nongenomic cortisol effects on human cognition and behavior. Future studies should continue to investigate the impact of rapid cortisol effects on the functioning of the human brain.
There is a lot of evidence for the impact of acute glucocorticoid treatment on hippocampus-dependent explicit learning and memory (memory for facts and events). But there have been few studies, investigating the effect of glucocorticoids on implicit learning and memory. We conducted three studies with different methodology to investigate the effect of glucocorticoids on different forms of implicit learning. In Study 1, we investigated the effect of cortisol depletion on short-term habituation in 49 healthy subjects. 25 participants received oral metyrapone (1500 mg) to suppress endogenous cortisol production, while 24 controls received oral placebo. Eye blink electromyogram (EMG) responses to 105 dB acoustic startle stimuli were assessed. Effective endogenous cortisol suppression had no effect on short-term habituation of the startle reflex, but startle eye blink responses were significantly increased in the metyrapone group. The latter findings are in line with previous human studies, which have shown that excess cortisol, sufficient to fully occupy central nervous system (CNS) corticosteroid receptors, may reduce startle eye blink. This effect may be mediated by CNS mechanisms controlling cortisol feedback. In Study 2, we investigated delay or trace eyeblink conditioning in a patient group with a relative hypocortisolism (30 patients with fibromyaligia syndrome/FMS) compared to 20 healthy control subjects. Conditioned eyeblink response probability was assessed by EMG. Morning cortisol levels, ratings of depression, anxiety and psychosomatic complaints as well as general symptomatology and psychological distress were assessed. As compared to healthy controls FMS patients showed lower morning cortisol levels, and trace eyeblink conditioning was facilitated whereas delay eyeblink conditioning was reduced. Cortisol measures correlate significantly only with trace eyeblink conditioning. Our results are in line with studies of pharmacologically induced hyper- and hypocortisolism, which affected trace eyeblink conditioning. We suggest that endocrine mechanisms affecting hippocampus-mediated forms of associative learning may play a role in the generation of symptoms in these patients.rnIn Study 3, we investigated the effect of excess cortisol on implicit sequence learning in healthy subjects. Oral cortisol (30 mg) was given to 29 participants, whereas 31 control subjects received placebo. All volunteers performed a 5-choice serial reaction time task (SRTT). The reaction speed of every button-press was determined and difference-scores were calculated as a proof of learning. Compared to the control group, we found a delayed learning in the cortisol group at the very beginning of the task. This study is the first human investigation, indicating impaired implicit memory function after exogenous administration of the stress hormone cortisol. Our findings support a previous neuroimaging study, which suggested that the medial temporal lobe (including the hippocampus) is also active in implicit sequence learning, but our results may also depend on the engagement of other brain structures.
In this thesis, three studies investigating the impact of stress on the protective startle eye blink reflex are reported. In the first study a decrease in prepulse inhibition of the startle reflex was observed after intravenous low dose cortisol application. In the second study a decrease in reflex magnitude of the startle reflex was observed after pharmacological suppression of endogenous cortisol production. In the third study, a higher reflex magnitude of the startle reflex was observed at reduced arterial and central venous blood pressure. These results can be interpreted in terms of an adaption to hostile environments.
The catechol-O-methyltransferase gene (COMT) plays a crucial role in the metabolism of catecholamines in the frontal cortex. A single nucleotide polymorphism (Val158Met SNP, rs4680) leads to either methionine (Met) or valine (Val) at codon 158, resulting in a three- to fourfold reduction in COMT activity. The aim of the present study was to assess the COMT Val158Met SNP as a risk factor for attention-deficit/hyperactivity disorder (ADHD), ADHD symptom severity and co-morbid conduct disorder (CD) in 166 children with ADHD. The main finding of the present study is that the Met allele of the COMT Val158Met SNP was associated with ADHD and increased ADHD symptom severity. No association with co-morbid CD was observed. In addition, ADHD symptom severity and early adverse familial environment were positive predictors of lifetime CD. These findings support previous results implicating COMT in ADHD symptom severity and early adverse familial environment as risk factors for co-morbid CD, emphasizing the need for early intervention to prevent aggressive and maladaptive behavior progressing into CD, reducing the overall severity of the disease burden in children with ADHD.
There is considerable evidence for an association between chronic dysregulation of the hypothalamus-pituitary adrenal (HPA) axis, atrophy of the hippocampus (HC) and cognitive and mood changes in clinical populations and in aging. The present thesis investigated this relationship in young healthy male subjects. Special emphasis was put on measures of HC volume and function derived from structural and functional magnetic resonance imaging (MRI). Higher cortisol levels after awakening were observed in subjects with higher levels of depressive symptomatology. Larger HC volume was associated with higher cortisol levels after awakening and in response to acute stress, whereas cognitive performance was impaired in subjects with larger HC volumes. Hippocampal activation during picture encoding was reduced after stress induction, and positive associations between activation and cognitive performance before stress were not present anymore afterwards. The present findings underscore the importance of structural and functional brain imaging for psychoneuroendocrinological research. The investigation of the association between cortisol levels and hippocampal integrity in young healthy subjects elicited unexpected results and adds to the understanding of HPA dysfunction and HC atrophy in clinical and aged populations.
Cognitive performance is contingent upon multiple factors. Beyond the impact of en-vironmental circumstances, the bodily state may hinder or promote cognitive processing. Af-ferent transmission from the viscera, for instance, is crucial not only for the genesis of affect and emotion, but further exerts significant influences on memory and attention. In particular, afferent cardiovascular feedback from baroreceptors demonstrated subcortical and cortical inhibition. Consequences for human cognition and behavior are the impairment of simple perception and sensorimotor functioning. Four studies are presented that investigate the mod-ulatory impact of baro-afferent feedback on selective attention. The first study demonstrates that the modulation of sensory processing by baroreceptor activity applies to the processing of complex stimulus configurations. By the use of a visual masking task in which a target had to be selected against a visual mask, perceptual interference was reduced when target and mask were presented during the ventricular systole compared to the diastole. In study two, selection efficiency was systematically manipulated in a visual selection task in which a target letter was flanked by distracting stimuli. By comparing participants" performance under homogene-ous and heterogeneous stimulus conditions, selection efficiency was assessed as a function of the cardiac cycle phase in which the targets and distractors were presented. The susceptibility of selection performance to the stimulus condition at hand was less pronounced during the ventricular systole compared to the diastole. Study one and two therefore indicate that inter-ference from irrelevant sensory input, resulting from temporally overlapping processing traces or from the simultaneous presentation of distractor stimuli, is reduced during phases of in-creased baro-afferent feedback. Study three experimentally manipulated baroreceptor activity by systematically varying the participant- body position while a sequential distractor priming task was completed. In this study, negative priming and distractor-response binding effects were obtained as indices of controlled and automatic distractor processing, respectively. It was found that only controlled distractor processing was affected by tonic increases in baro-receptor activity. In line with study one and two these results indicate that controlled selection processes are more efficient during enhanced baro-afferent feedback, observable in dimin-ished aftereffects of controlled distractor processing. Due to previous findings that indicated baro-afferent transmission to affect central, rather than response-related processing stages, study four measured lateralized-readiness potentials (LRPs) and reaction times (RTs), while participants, again, had to selectively respond to target stimuli that were surrounded by dis-tractors. The impact of distractor inhibition on stimulus-related, but not on response-related LRPs suggests that in a sequential distractor priming task, the sensory representations of dis-tractors, rather than motor responses are targeted by inhibition. Together with the results from studies one through three and the finding of baroreceptor-mediated behavioral inhibition tar-geting central processing stages, study four corroborates the presumption of baro-afferent signal transmission to modulate controlled processes involved in selective attention. In sum, the work presented shows that visual selective attention benefits from in-creased baro-afferent feedback as its effects are not confined to simple perception, but may facilitate the active suppression of neural activity related to sensory input from distractors. Hence, due to noise reduction, baroreceptor-mediated inhibition may promote effective selec-tion in vision.
The role of cortisol and cortisol dynamics in patients after aneurysmal subarachnoid hemorrhage
(2011)
Spontaneous aneurysmal subarachnoid hemorrhage (SAH) is a form of stroke which constitutes a severe trauma to the brain and often leads to serious long-term medical and psychosocial sequels which persist for years after the acute event. Recently, adrenocorticotrophic hormone deficiency has been identified as one possible consequence of the bleeding and is assumed to occur in around 20% of all survivors. Additionally, a number of studies report a high prevalence of post-SAH symptoms such as lack of initiative, fatigue, loss of concentration, impaired quality of life and psychiatric symptoms such as depression. The overlap of these symptoms and those of patients with untreated partial or complete hypopituitarism lead to the suggestion that neuroendocrine dysregulations may contribute to the psychosocial sequels of SAH. Therefore, one of the aims of this work is to gain insights into the role of neuroendocrine dysfunction on quality of life and the prevalence of psychiatric sequels in SAH-patients. Additionally, as data on cortisol dynamics after SAH are scarce, diurnal cortisol profiles are investigated in patients in the acute and chronic phase, as well as the cortisol awakening response and feedback sensitivity in the chronic phase after SAH. As a result, it can be shown that some SAH patients exhibit lower serum cortisol levels but at the same time a higher cortisol awakening response in saliva than healthy controls. Also, patients in the chronic phase after SAH do have a stable diurnal cortisol rhythm while there are disturbances in around 50% of all patients in the acute phase, leading to the conclusion that a single baseline measurement of cortisol is of no substantial use for diagnosing cortisol dysregulations in the acute phase after SAH. It is assumed that in SAH patients endocrine changes occur over time and that a combination of adrenal exhaustion and a subsequent downregulation of corticosteroid binding globulin may be the most probable causes for the dissociation of serum cortisol concentrations and salivary cortisol profiles in the investigated SAH patients. These changes may be an emergency response after SAH and, as elevated free cortisol levels are connected to a better psychosocial outcome in patients in the chronic phase after SAH, this reaction may even be adaptive.
The influence of affect on vocal parameters has been well investigated in speech portrayed by actors, but little is known about affect expression in more natural or authentic speech behavior. This is partly due to the difficulty of generating speech samples that represent authentic expression of speaker affect. The present work investigates the influence of speaker affect on the vocal fundamental frequency (F0) in comparatively authentic speech samples. Three well-documented psychophysiological research methods were applied for the induction of affective states in German native speakers in order to obtain speech samples with authentic affect expression: the Cold Pressor Test (CPT), the Stroop Color-Word Test (SCWT) and the presentation of slides from the International Affective Pictures System (IAPS). The here reported results show that the influence of affect on F0 is differentially modulated by psychophysiological processes as well as socio-cultural influences. They also indicate that this approach may be useful for future research and further to gain a deeper understanding of authentic vocal affect expression. Moreover, F0 may constitute an additional non-invasive, easy to obtain measure for the established psychophysiological research methodology.
Repeatedly encountering a stimulus biases the observer’s affective response and evaluation of the stimuli. Here we provide evidence for a causal link between mere exposure to fictitious news reports and subsequent voting behavior. In four pre-registered online experiments, participants browsed through newspaper webpages and were tacitly exposed to names of fictitious politicians. Exposure predicted voting behavior in a subsequent mock election, with a consistent preference for frequent over infrequent names, except when news items were decidedly negative. Follow-up analyses indicated that mere media presence fuels implicit personality theories regarding a candidate’s vigor in political contexts. News outlets should therefore be mindful to cover political candidates as evenly as possible.
Ability self-concept (SC) and self-efficacy (SE) are central competence-related self-perceptions that affect students’ success in educational settings. Both constructs show conceptual differences but their empirical differentiation in higher education has not been sufficiently demonstrated. In the present study, we investigated the empirical differentiation of SC and SE in higher education with N = 1,243 German psychology students (81% female; age M = 23.62 years), taking into account central methodological requirements that, in part, have been neglected in prior studies. SC and SE were assessed at the same level of specificity, only cognitive SC items were used, and multiple academic domains were considered. We modeled the structure of SC and SE taking into account a multidimensional and/or hierarchical structure and investigated the empirical differentiation of both constructs on different levels of generality (i.e., domain-specific and domain-general). Results supported the empirical differentiation of SC and SE with medium-sized positive latent correlations (range r = .57 - .68) between SC and SE on different levels of generality. The knowledge about the internal structure of students’ SC and SE and the differentiation of both constructs can help us to develop construct-specific and domain-specific intervention strategies. Future empirical comparisons of the predictive power of SC and SE can provide further evidence that both represent empirical different constructs.
Educational researchers have intensively investigated students" academic self-concept (ASC) and self-efficacy (SE). Both constructs are part of the competence-related self-perceptions of students and are considered to support students" academic success and their career development in a positive manner (e.g., Abele-Brehm & Stief, 2004; Richardson, Abraham, & Bond, 2012; Schneider & Preckel, 2017). However, there is a lack of basic research on ASC and SE in higher education in general, and in undergraduate psychology courses in particular. Therefore, according to the within-network and between-network approaches of construct validation (Byrne, 1984), the present dissertation comprises three empirical studies examining the structure (research question 1), measurement (research question 2), correlates (research question 3), and differentiation (research question 4) of ASC and SE in a total sample of N = 1243 psychology students. Concerning research question 1, results of confirmatory factor analysis (CFAs) implied that students" ASC and SE are domain-specific in the sense of multidimensionality, but they are also hierarchically structured, with a general factor at the apex according to the nested Marsh/Shavelson model (NMS model, Brunner et al., 2010). Additionally, psychology students" SE to master specific psychological tasks in different areas of psychological application could be described by a 2-dimensional model with six factors according to the Multitrait-Multimethod (MTMM)-approach (Campbell & Fiske, 1959). With regard to research question 2, results revealed that the internal structure of ASC and SE could be validly assessed. However, the assessment of psychology students" SE should follow a task-specific measurement strategy. Results of research question 3 further showed that both constructs of psychology students" competence-related self-perceptions were positively correlated to achievement in undergraduate psychology courses if predictor (ASC, SE) corresponded to measurement specificity of the criterion (achievement). Overall, ASC provided substantially stronger relations to achievement compared to SE. Moreover, there was evidence for negative paths (contrast effects) from achievement in one psychological domain on ASC of another psychological domain as postulated by the internal/external frame of reference (I/E) model (Marsh, 1986). Finally, building on research questions 1 to 3 (structure, measurement, and correlates of ASC and SE), psychology students" ASC and SE were be differentiated on an empirical level (research question 4). Implications for future research practices are discussed. Furthermore, practical implications for enhancing ASC and SE in higher education are proposed to support academic achievement and the career development of psychology students.
The forward testing effect is an indirect benefit of retrieval practice. It refers to the finding that retrieval practice of previously studied information enhances learning and retention of subsequently studied other information in episodic memory tasks. Here, two experiments were conducted that investigated whether retrieval practice influences participants’ performance in other tasks, i.e., arithmetic tasks. Participants studied three lists of words in anticipation of a final recall test. In the testing condition, participants were immediately tested on lists 1 and 2 after study of each list, whereas in the restudy condition, they restudied lists 1 and 2 after initial study. Before and after study of list 3, participants did an arithmetic task. Finally, participants were tested on list 3, list 2, and list 1. Different arithmetic tasks were used in the two experiments. Participants did a modular arithmetic task in Experiment 1a and a single-digit multiplication task in Experiment 1b. The results of both experiments showed a forward testing effect with interim testing of lists 1 and 2 enhancing list 3 recall in the list 3 recall test, but no effects of recall testing of lists 1 and 2 for participants’ performance in the arithmetic tasks. The findings are discussed with respect to cognitive load theory and current theories of the forward testing effect.
Long-Term Memory Updating: The Reset-of-Encoding Hypothesis in List-Method Directed Forgetting
(2017)
People- memory for new information can be enhanced by cuing them to forget older information, as is shown in list-method directed forgetting (LMDF). In this task, people are cued to forget a previously studied list of items (list 1) and to learn a new list of items (list 2) instead. Such cuing typically enhances memory for the list 2 items and reduces memory for the list 1 items, which reflects effective long-term memory updating. This review focuses on the reset-of-encoding (ROE) hypothesis as a theoretical explanation of the list 2 enhancement effect in LMDF. The ROE hypothesis is based on the finding that encoding efficacy typically decreases with number of encoded items and assumes that providing a forget cue after study of some items (e.g., list 1) resets the encoding process and makes encoding of subsequent items (e.g., early list 2 items) as effective as encoding of previously studied (e.g., early list 1) items. The review provides an overview of current evidence for the ROE hypothesis. The evidence arose from recent behavioral, neuroscientific, and modeling studies that examined LMDF on both an item and a list level basis. The findings support the view that ROE plays a critical role for the list 2 enhancement effect in LMDF. Alternative explanations of the effect and the generalizability of ROE to other experimental tasks are discussed.
List-method directed forgetting (LMDF) is the demonstration that people can intentionally forget previously studied information when they are asked to forget what they have previously learned and remember new information instead. In addition, recent research demonstrated that people can selectively forget when cued to forget only a subset of the previously studied information. Both forms of forgetting are typically observed in recall tests, in which the to-be-forgotten and to-be-remembered information is tested independent of original cuing. Thereby, both LMDF and selective directed forgetting (SDF) have been studied mostly with unrelated item materials (e.g., word lists). The present study examined whether LMDF and SDF generalize to prose material. Participants learned three prose passages, which they were cued to remember or forget after the study of each passage. At the time of testing, participants were asked to recall the three prose passages regardless of original cuing. The results showed no significant differences in recall of the three lists as a function of cuing condition. The findings suggest that LMDF and SDF do not occur with prose material. Future research is needed to replicate and extend these findings with (other) complex and meaningful materials before drawing firm conclusions. If the null effect proves to be robust, this would have implications regarding the ecological validity and generalizability of current LMDF and SDF findings.
The forward effect of testing refers to the finding that retrieval practice of previously studied information increases retention of subsequently studied other information. It has recently been hypothesized that the forward effect (partly) reflects the result of a reset-of-encoding (ROE) process. The proposal is that encoding efficacy decreases with an increase in study material, but testing of previously studied information resets the encoding process and makes the encoding of the subsequently studied information as effective as the encoding of the previously studied information. The goal of the present study was to verify the ROE hypothesis on an item level basis. An experiment is reported that examined the effects of testing in comparison to restudy on items’ serial position curves. Participants studied three lists of items in each condition. In the testing condition, participants were tested immediately on non-target lists 1 and 2, whereas in the restudy condition, they restudied lists 1 and 2. In both conditions, participants were tested immediately on target list 3. Influences of condition and items’ serial learning position on list 3 recall were analyzed. The results showed the forward effect of testing and furthermore that this effect varies with items’ serial list position. Early target list items at list primacy positions showed a larger enhancement effect than middle and late target list items at non-primacy positions. The results are consistent with the ROE hypothesis on an item level basis. The generalizability of the ROE hypothesis across different experimental tasks, like the list-method directed-forgetting task, is discussed.
The distractor-response binding effect (Frings & Rothermund, 2011; Frings, Rothermund, & Wentura, 2007; Rothermund, Wentura, & De Houwer, 2005) is based on the idea that irrelevant information will be integrated with the response to the relevant stimuli in an episodic memory trace. The immediate re-encounter of any aspect of this saved episode " be it relevant or irrelevant " can lead to retrieval of the whole episode. As a consequence, the previously executed and now retrieved response may influencing the response to the current relevant stimulus. That is, the current response may either be facilitated or be impaired by the retrieved response, depending on whether it is compatible or incompatible to the currently demanded response. Previous research on this kind of episodic retrieval focused on the influence on action control. I examined if distractor response binding also plays a role in decision making in addition to action control. To this end I adapted the distractor-to-distractor priming paradigm (Frings et al., 2007) and conducted nine experiments in which participants had to decide as fast as possible which disease a fictional patient suffered from. To infer the correct diagnosis, two cues were presented; one did not give any hint for a disease (the irrelevant cue), whereas the other did (the relevant cue). Experiments 1a to 1c showed that the distractor-response binding effect is present in deterministic decision situations. Further, experiments 2a and 2b indicate that distractor-response binding also influences decisions under uncertainty. Finally, experiments 3a to 3d were conducted to test some constraints and underlying mechanisms of the distractor-response binding effect in decision making under uncertainty. In sum, these nine experiments provide strong evidence that distractor-response binding influences decision making.
COVID-19 was a harsh reminder that diseases are an aspect of human existence and mortality. It was also a live experiment in the formation and alteration of disease-related attitudes. Not only are these attitudes relevant to an individual’s self-protective behavior, but they also seem to be associated with social and political attitudes more broadly. One of these attitudes is Social Darwinism, which holds that a pandemic benefits society by enabling nature “to weed out the weak”. In two countries (N = 300, N = 533), we introduce and provide evidence for the reliability, validity, and usefulness of the Disease-Related Social Darwinism (DRSD) Short Scale measuring this concept. Results indicate that DRSD is meaningful related to other central political attitudes like Social Dominance Orientation, Authoritarianism and neoliberalism. Importantly, the scale significantly predicted people’s protective behavior during the Pandemic over and above general social Darwinism. Moreover, it significantly predicted conservative attitudes, even after controlling for Social Dominance Orientation.
On the Influence of Ignored Stimuli: Generalization and Application of Distractor-Response Binding.
(2011)
In selection tasks where target stimuli are accompanied by distractors, responses to target stimuli, target stimuli and the distractor stimuli can be encoded together as one episode in memory. Subsequent repetition of any aspect of such an episode can lead to the retrieval of the whole episode including the response. Thus, repeating a distractor can retrieve responses given to previous targets; this mechanism was labeled distractor-response binding and has been evidenced in several visual setups. Three experiments of the present thesis implemented a priming paradigm with an identification task to generalize this mechanism to auditory and tactile stimuli as well as to stimulus concepts. In four more experiments the possible effect of distractor-response binding on drivers' reactions was investigated. The same paradigm was implemented using more complex stimuli, foot responses, go/no-go responses, and a dual task setup with head-up and head-down displays. The results indicate that distractor-response binding effects occur with auditory and tactile stimuli and that the process is mediated by a conceptual representation of the distractor stimuli. Distractor-response binding effects also revealed for stimuli, responses, and framework conditions likely to occur in a driving situation. It can be concluded that the effect of distractor-response binding needs to be taken into account for the design of local danger warnings in driver assistance systems.
By rodent studies it has been shown that the mineralocorticoid receptor (MR) is a candidate gene for the investigation of cognitive functions comparable to human executive function. The present work addresses the question if polymorphisms in the MR gene can act as a "probe" to explain a part of the interindividual variance of human executive functions. For this purpose, 72 healthy young participants were assigned to four equally sized groups, concerning their particular MR genotype for two common MR polymorphisms. They were investigated in an electroencephalogram (EEG) test session, accomplishing two cognitive tests while delivering saliva samples for subsequent cortisol measures. The two tests chosen for the assessment of executive functions were the Attention Network Task (ANT) and a modified version of the Wisconsin Card Sorting Test (WCST).Chapter 1 of the present work reports of the rational bases for the empirical approach, which were built up on a broad theoretical background presented in Chapter 2. In the third chapter, the investigation and results of the statistical analysis for behavioral data (i.e. reaction times, accuracy/error rates) are presented. No association with MR polymorphisms was found for the reaction times of both tests. For the accuracy rate, differences between genotype groups were found for ANT and WCST, indicating an association of MR polymorphisms and accuracy in the Alertness and Executive Control network of the ANT and during the detection of an intradimensional shift in the WCST. Data acquisition and the results for EEG data analyses are presented in Chapter 4. The results show that groups differing for MR genotype show different activity over prefrontal motor areas during the process of answering to the ANT. Those group differences again were prominent for the Alertness and Executive Control network. A tendency for further significant group differences was found for activity on frontopolar positions in extradimensional rule switching. Chapter 5 summarizes the findings for the analysis of salivary free cortisol, showing a tendency for an association between MR polymorphisms and a mildly stimulated Hypothalamus-pituitary-adrenal (HPA) axis during the test situation. The results of the different measures are integrated and discussed in Chapter 6 within the scope of novel findings in investigating the functionality of the chosen MR polymorphisms. Finally, Chapter 7 gives an outlook on the methodology and constraints of future research strategies to further describe the role of the MR in human cognitive function.
The aim of the thesis was to investigate the role of the immune system in fibromyalgia (FM), as part of a dynamic co-regulation between different bodily systems. FM is a chronic musculoskeletal disorder characterized by widespread pain and specific tender points, combined with other symptoms including fatigue, sleep disturbances, morning stiffness and anxiety. The main goal of the work was to identify possible dysregulation of peripheral immune and endocrine parameters in patients with FM compared to matched healthy controls. Moreover, the possible relation between symptom complaints and the specific parameters measured was also evaluated. A first approach was to investigate possible differences between FM patients and controls in the expression of cytokines, as they have been implicated in the occurrence of several of the symptoms associated with FM. Furthermore, adhesion molecules which are involved in cell-to-cell communication and immune cell trafficking were also studied. The latter are known to be regulated by both cytokines and glucocorticoids (GCs) and their expression is often found altered in patients with immune dysregulation. It was expected that subjects with FM would have an increased production of proinflammatory cytokines and/or a reduced antiinflammatory cytokine production and that certain cytokines and/or adhesion molecules would be differently regulated by dexamethasone (DEX). Unstimulated blood was used in the analysis of adhesion molecule expression by flow cytometry while stimulated whole blood cell cultures were used in cytokine flow cytometry assays. Peripheral blood mononuclear cells (PBMCs) were also cultured and the supernatants collected to determine the concentration of cytokines by biochip protein array. In addition, serum samples were used in enzyme-linked immunosorbent assays (ELISA) for quantification of soluble adhesion molecules. L-selectin was found elevated on monocytes and neutrophils of FM patients. A bias toward lower IL-4 levels was observed in FM patients. Based on studies showing differences in glucocorticoid receptor (GR) affinity and disturbances associated with loss of hypothalamic-pituitary-adrenal (HPA) axis resiliency in FM, it was hypothesized whether FM would be associated with abnormalities in glucocorticoid sensitivity. Total plasma cortisol and salivary free cortisol were quantified by ELISA and time-resolved fluorescence immunoassay, respectively. GR sensitivity through DEX inhibition of IL-6, in stimulated whole blood, was evaluated after cytokine quantification by ELISA. The corticosteroid receptors, GR alpha and mineralocorticoid receptor (MR), as well as the glucocorticoid-induced leucine zipper (GILZ) and the FK506 binding protein 5 mRNA expression were assessed in PBMCs by real-time reverse transcription-polymerase chain reaction (RT-PCR). Furthermore, sequencing of RT-PCR products and/or genomic DNA was used for mutational analysis of the corticosteroid receptors. We observed lower basal plasma cortisol levels (borderline statistical significance) and a lower expression of corticosteroid receptors and GILZ in FM patients when compared to healthy controls. The minor allele of the MR single nucleotide polymorphism (SNP) rs5522 was found more often in FM patients than in controls. In addition, female carriers of this SNP seemed to have reduced salivary cortisol responses to a strong psychological stressor (Trier Social Stress Test) compared to non-carriers. FM patient carriers of an MR intronic SNP (rs17484245), before exon 3, were associated with significantly higher scores of depression symptoms compared to patient non-carriers. The thesis includes also a comprehensive analysis of the complexity of GR regulation and the role of alternative mRNA splicing. It focuses on the differential expression of the untranslated GR first exons, their high sequence homology among different species and how genetic determinants, without apparent relevance, may have implications in health and disease. In FM patients, GR exon 1-C expression was found lower and a significant difference was observed when comparing GR 1-C expression between antidepressant-free and patients who had taken antidepressants until two weeks before sample collection. In summary, the study shows a slight disturbance of some components of the innate immune system of FM patients and suggests an enhanced adhesion and possible recruitment of leukocytes to inflammatory sites. The reduced expression of corticosteroid receptors and possibly the reduced MR function may be associated with an impaired function of the HPA axis in these patients. A hyporesponsiveness of the HPA axis under stress or disturbances of the stress response could make these patients more vulnerable to cytokines and inflammation which, compounded by lower antiinflammatory mediators, may sustain some of the symptoms that contribute to the clinical picture of FM.